Old genes: how the genetics of aging may play a role in Parkinson’s disease.

or technically,

Distinct cellular and molecular environments support aging-related DNA methylation changes in the substantia nigra.

[See Original Abstract on Pubmed]

Authors of the study: Maria Fasolino, Shuo Liu, Yinsheng Wang and Zhaolan Zhou

Have you ever wondered about the cause of Parkinson’s disease and what researchers are doing to improve treatment? First described in the 1800s, this devastating neurological disorder is currently estimated to affect seven to ten million people worldwide (with some of the more recognizable victims including Michael J. Fox, Muhammad Ali, and Robin Williams). Symptoms of the disease include motor dysfunction (shaking, rigidity, difficulty walking, etc), depression, and dementia. Although there are ways to slow disease progression, there is presently no cure available, and the average life expectancy is only 7-14 years after diagnosis. We still have a lot to learn about what makes certain people susceptible to the disorder and how we can improve treatment options. With this in mind, UPenn neuroscience graduate student Maria Fasolino and her team in the Zhou lab set out to learn more about what changes take place in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. during aging that might correlate to the development of Parkinson’s disease.

Doctors have known what the brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. of Parkinson’s disease patients look like for a long time. The disease causes brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. cells (neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles) in the substantia nigra, which is a brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. area important for controlling movement, to die. Unfortunately, how this happens is still a mystery, and doctors aren’t sure why the substantia nigra is particularly susceptible. Scientists are taking a closer look at our DNA for more clues about the disease. The DNA inside each of our cells tells them what proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. to “print,” and you can think of proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. as the essential machinery of a cell executing its critical functions (enzymes, receptorsA protein on a cell’s surface that binds to specific molecules (i.e. other proteins or chemicals). Typically, a receptor is said to fit with its partner molecule(s) like a lock and key. When bound by the right molecule, receptors often transmit signals to the rest of the cell. and more). Your DNA is passed down from your parents, and scientists used to think that DNA did not change after being inherited (that is, the DNA you’re born with is the DNA you have for life). Over the last few decades, however, geneticists have realized that our DNA can actually be modified by our environment over the course of our lifetime. These chemical modifications to an individual’s DNA are referred to as epigenetics (epi=“on top of”; genetics=“genesA unit of DNA that encodes a protein and tells a cell how to function,” or DNA), and previous research has shown that epigenetic modification onto DNA accumulates over one’s lifetime, particularly in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Changes to DNA alter its ability to print proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies., and thus can drastically affect the function or survival of a cell. Maria’s main goal was to see if old age causes any epigenetic oddities in the substantia nigra (the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region implicated in Parkinson’s).

One of the many ways DNA can be modified is by a process known as methylation (a direct, chemical modification onto one of the building blocks of DNA). As mentioned above, DNA modifications such as methylation have the ability to affect how certain genesA unit of DNA that encodes a protein and tells a cell how to function are regulated and which proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. are made by a cell. Recently, researchers discovered that these modifications, such as methylation, aren’t as permanent as they thought. These ‘earmarks’ on our DNA can be kept, erased, or modified into a completely different type of modification, and this entire process can be quite dynamic throughout life!

Maria looked at aging mice to more closely study how the epigenetics of their substantia nigra cells may be changing over time. She found that the methylation marks on the DNA of these substantia nigra cells were much less stable with age when compared to a different brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. area not affected by Parkinson’s. Furthermore, she went on to show that this methylation difference is specific to dopamine neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles, which are the cells in the substantia nigra implicated in Parkinson’s disease. It is not yet clear whether this different epigenetic pattern in the substantia nigra is what makes it particularly susceptible to cell death with aging. This epigenetic effect might be influenced by the presence of proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. that methylate DNA (DNMTs) or those that erase methylation (TETs), which could potentially serve as targets for treatment or early detection of the disease. Maria’s study provides us with more information about the cells in the substantia nigra and how they change with age, giving researchers novel insights on why Parkinson’s may specifically target this region of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Millions of people worldwide suffer from Parkinson’s disease, but engineering treatments that target epigenetic marks like methylation could potentially stop Parkinson’s in it tracks.
About the brief writer: Dan Kalamarides  Dan is a third year student still amazed that we can record activity of a single, live neuron. He studies the role of inhibitory plasticity in the addictive properties of opioids and other drugs.

About the brief writer: Dan Kalamarides

Dan is a third year student still amazed that we can record activity of a single, live neuron. He studies the role of inhibitory plasticity in the addictive properties of opioids and other drugs.

Interested in learning more about the epigenetics of aging? Take a look at Maria’s full paper here!


NGG GLIAneurodegeneration